rs432085

Positions:

• chr3-191381679-T-C
• chr3-191381679-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_178335.3(CCDC50):​c.1242+747T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.648 in 152,014 control chromosomes in the GnomAD database, including 33,809 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.65 (33809 hom., cov: 32)
• Consequence: CCDC50 NM_178335.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.183

Genes affected

CCDC50 (HGNC:18111): (coiled-coil domain containing 50) This gene encodes a soluble, cytoplasmic, tyrosine-phosphorylated protein with multiple ubiquitin-interacting domains. Mutations in this gene cause nonsyndromic, postlingual, progressive sensorineural DFNA44 hearing loss. In mouse, the protein is expressed in the inner ear during development and postnatal maturation and associates with microtubule-based structures. This protein may also function as a negative regulator of NF-kB signaling and as an effector of epidermal growth factor (EGF)-mediated cell signaling. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Oct 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.894 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC50	NM_178335.3	c.1242+747T>C		intron_variant		ENST00000392455.9	NP_848018.1
CCDC50	NM_174908.4	c.714+747T>C		intron_variant			NP_777568.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC50	ENST00000392455.9	c.1242+747T>C		intron_variant		1	NM_178335.3	ENSP00000376249.4
CCDC50	ENST00000392456.4	c.714+747T>C		intron_variant		1		ENSP00000376250.4

Frequencies

GnomAD3 genomes AF: 0.648 AC: 98445 AN: 151896 Hom.: 33747 Cov.: 32

Gnomad AFR AF: 0.855

Gnomad AMI AF: 0.347

Gnomad AMR AF: 0.680

Gnomad ASJ AF: 0.543

Gnomad EAS AF: 0.916

Gnomad SAS AF: 0.693

Gnomad FIN AF: 0.565

Gnomad MID AF: 0.608

Gnomad NFE AF: 0.515

Gnomad OTH AF: 0.603

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.648 AC: 98566 AN: 152014 Hom.: 33809 Cov.: 32 AF XY: 0.656 AC XY: 48745 AN XY: 74318

Gnomad4 AFR AF: 0.855

Gnomad4 AMR AF: 0.681

Gnomad4 ASJ AF: 0.543

Gnomad4 EAS AF: 0.916

Gnomad4 SAS AF: 0.693

Gnomad4 FIN AF: 0.565

Gnomad4 NFE AF: 0.515

Gnomad4 OTH AF: 0.602

Alfa AF: 0.547 Hom.: 31402

Bravo AF: 0.667

Asia WGS AF: 0.808 AC: 2803 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	5.2
DANN	Benign	0.55

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs432085; hg19: chr3-191099468;